PROJECT SUMMARY The transformation of alkenes into precursors for natural products is an important step in many pharmaceutical processes. In many cases, only one enantiomer of a natural product or pharmaceutical compound has the intended biological activity. Other enantiomers may be inactive, and thus a waste of material, or cause dangerous unwanted side-effects. However, the synthesis of enantiopure bioactive molecules can be difficult and costly. Enantioselective variants of some of the most important molecular complexity-building reactions, like the Diels-Alder cycloaddition and hydrofunctionalization reaction, are limited in substrate scope and scale-up ability. The polarity inverted radical cation reaction greatly expanded the substrate scope and the advent of visible light photocatalysis provided a cost-effective method to catalyze these reactions. Few asymmetric photocatalytic methodologies have been developed with limited application to natural product and pharmaceutical synthesis. The proposed research will develop an asymmetric co-catalytic methodology general to photocatalyzed radical cation reactions. This methodology will take advantage of ion-pair formation between the radical cation and a counteranion in solution. Chiral hydrogen bond donor co-catalysts that bind the counteranions will provide a means to optimize the asymmetric reaction independent of the photocatalyst yielding unparalleled control over the reaction rate and selectivity. This methodology will be initially optimized for the photoinitiated radical cation Diels-Alder cycloaddition. Separate optimization of the photocatalyst and the hydrogen bond donating co-catalysts will provide a synthetically useful asymmetric transformation. Application of this methodology to the synthesis of enantiopure indolines will provide clear evidence of its applicability in the synthesis of biologically important compounds and scaffolds. The proposed methodology will be translated to the asymmetric photocatalysis of alkene hydrofunctionalization to provide enantiopure value-added products. The successful development of this asymmetric co-catalytic methodology will provide chemists with the means to rapidly synthesize enantiopure compound libraries for rapid drug screening and development. The training I receive through the proposed research and mentorship from Professor Tehshik Yoon will provide me with an extensive background in organic synthesis and methodology development. Through combination with my background in spectroscopy and photochemistry I will develop an independent career as an R1 university professor focused on the use of mechanistic study to develop novel, pharmaceutically useful organic transformation.